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Particuology 2014年第6期12卷 74-80页

作者： Yuying Liu Xiaoming Chen Lianyan Wang tingyuan yang Qipeng Yuan Guanghui Ma National Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of Sciences State Key Laboratory of Chemical Resource Engineering College of Life Science and TechnologyBeijing University of Chemical Technology University of Chinese Academy of Sciences

The use of microparticles（MPs） as adjuvants has attracted increasing interest in vaccine delivery *** physiochemical characteristics of MPs including hydrodynamic size,surface properties,and morphology can regulate the immune *** charge is an important characteristic of MPs,but how it affects their adjuvanticity remains *** this study,we prepared uniform-sized polylactide MPs coated with various polymers of different positive charge,and investigated how the surface charge affected antigen loading and macrophage phagocytosis and activation in vitro.A higher surface charge greatly enhanced antigen loading and antigen internalization into macrophages,promoted the expression of MHC 11 and CD80,and increased the secretion level of *** together,these results indicated that surface charge was an important parameter for improving the adjuvanticity of MPs.

关键词： Microparticle(MP) Macrophage Surface charge Antigen loading Phagocytosis Activation

Dual-function baicalin and baicalin-loaded poly（lactic-co-glycolic acid） nanoparticles： Immune activation of dendritic cells and arrest of the melanoma cell cycle at the G2/M phase

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Particuology 2018年第2期16卷 64-71页

作者： Huimei Wang Shulan Han Lianyan Wang tingyuan yang Guifeng Zhang Lian Yu Yue Zhao Key Laboratory of Forest Plant Ecology Ministry of Education Northeast Forestry University Harbin 150040 China National Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing 100190 China College of PharmacyJiamusi University Jiamusi 154000 China Epithelial Systems Biology Laboratory Systems Biology Center National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892-1603. USA

Accumulating evidence suggests that the flavone glycoside baicalin has immunomodulatory effects and antitumor potential. However, its weak stability in solution, poor absorption, and low bioavailability limit its clinical application. To overcome these disadvantages, we developed baicalin-loaded poly（lactic-co-glycolic acid） nanoparticles （PLGA-B） of small size. Next, we evaluated the dual function of immunotherapy and chemotherapy for PLGA-B using immune-related cells and tumor cells. Results showed that PLGA-B were spherical, with a particle size -120 nm and narrow size distribution with an excellent polydispersity index of 0.103. In vitro experiments revealed that baicalin and PLGA-B could activate dendritic cells （DCs） to have higher expression of surface marker molecules and costimulatory molecules than those of control cells. Baicalin and PLGA-B could trigger apoptosis in melanoma （B16） cells via cell-cycle arrest at the G2/M phase. These data suggest that PLGA-B have important roles in activating DCs and killing melanoma cells. Our study could lay a foundation for melanoma treatment through a combined strategy of immunotherapy and chemotherapy.

关键词： Baicalin Baicalin-loaded PLGA nanoparticles Dendritic cells activation Anti-tumor

Optimization and evaluation of fish oil rnicrocapsules

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Particuology 2016年第6期14卷 162-168页

作者： Hui Liu Lia nyan Wang tingyuan yang Guifeng Zhang Jian Huang Jing Sun Junsheng Huo Division of Food Science & Technology National Institute for Nutrition and Health Chinese Center for Disease Control and Prevention Beijing 100050China National Key Lab of Biochemical Engineering Institute of Process Engineering Chinese Academy of Science Beifing 100190 China

Fish oil microcapsules were prepared using two natural polysaccharides, alginate and chitosan, as the wall materials. A response surface methodology （RSM） was used to optimize the conditions for fish oil encapsulation efficiency （FOEE）. The FOEE was investigated with respect to three key-variables in the RSM： ratio of inner oil phase to aqueous phase （X1 w/w）; concentration of the aqueous phase （X2, wt%）; and ratio of the aqueous phase to outer oil phase （X3, v/v）. The optimal formulation obtained from the RSM model, i.e., 2.7：1 （X1）, 1.6 wt% （X2）, and 11.5：1 （X3）, gave a FOEE of 28%. The model was validated and the fish oil microcapsules prepared under the optimized conditions were characterized in terms of particle size, polydispersity index （PDI）, zeta potential, surface morphology, and in vitro release. The average droplet size, PDI, and zeta potential were 915 nm, 0.038, and ＋5.2 mV, respectively. The fish oil microcapsules were highly uniform microspheres, and had an accumulative release rate of 77.7% in 270 min in a gastrointestinal model, indicating their potential as an alternative carrier for the controlled release of fish oil. In conclusion, formulating optimal microencapsulation conditions by the RSM can be applied to the microencapsulation of various oil-soluble nutrients for food applications.

关键词： Optimization Microencapsulation Fish oil Evaluation Response surface methodology

Evaluating the relative importance of predictors in Generalized Additive Models using the *** R package

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Plant Diversity 2024年第4期46卷 542-546页

作者： Jiangshan Lai Jing Tang tingyuan Li Aiying Zhang Lingfeng Mao College of Ecology and Environment Nanjing Forestry UniversityNanjing210037China Research Center of Quantitative Ecology Nanjing Forestry UniversityNanjing 210037China University of Chinese Academy of Sciences Beijing100049China Guangzhou Climate and Agro-meteorology Center Guangzhou 511430China Guangdong Ecological Meteorological Center Guangzhou 510640China

Generalized Additive Models(GAMs)are widely employed in ecological research,serving as a powerful tool for ecologists to explore complex nonlinear relationships between a response variable and ***,evaluating the relative importance of predictors with concurvity(analogous to collinearity)on response variables in GAMs remains a *** address this challenge,we developed an R package named *** calculates individual R^(2) values for predictors,based on the concept of'average shared variance',a method previously introduced for multiple regression and canonical *** these individual R^(2)s,which add up to the overall R^(2),researchers can evaluate the relative importance of each predictor within *** illustrate the utility of the *** package by evaluating the relative importance of emission sources and meteorological factors in explaining ozone concentration variability in air quality data from London,*** believe that the *** package will improve the interpretation of results obtained from GAMs.

关键词： Average shared variance Coefficient of determination Commonality analysis GAMs Hierarchical partitioning Individual R^(2)

Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin

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Asian Journal of Pharmaceutical Sciences 2014年第3期9卷 129-136页

作者： Tongtong Ma Lianyan Wang tingyuan yang Guanghui Ma Siling Wang Department of Pharmaceutics Shenyang Pharmaceutical UniversityShenyangPR China National Key Laboratory of Biochemical Engineering PLA Key Laboratory of Biopharmaceutical Production&Formulation EngineeringInstitute of Process EngineeringChinese Academy of SciencesBeijingPR China

In this study,a polymeric lipid nanoparticle(NP)(simplified as Lipid NP)was reported as a promising oral vaccine delivery *** Lipid NPs composed of a hydrophobic polymeric poly(D,L-lactide-co-glycolide)(PLGA)core and a surface coating of lipid *** emulsification technique was used to obtain uniform-sized Lipid ***(OVA)was used as a model *** with the pure PLGA NPs,the Lipid NPs achieved higher loading capacity(LC)and entrapment efficiency(EE)for the encapsulated *** in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal(GI)environment for a long *** addition,a human microfold cell(M-cell)transcytotic assay demonstrated that due to a lipid layer structure on the particle surface,the Lipid NPs showed higher affinity to the *** the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells,the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.

关键词： Oral delivery Vaccine Polymeric lipid nanoparticle M-cell affinity

Design, synthesis, molecular modeling, and biological evaluation of acrylamide derivatives as potent inhibitors of human dihydroorotate dehydrogenase for the treatment of rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2021年第3期11卷 795-809页

作者： Fanxun Zeng Shiliang Li Guantian yang Yating Luo Tiantian Qi Yingfan Liang tingyuan yang Letian Zhang Rui Wang Lili Zhu Honglin Li Xiaoyong Xu Shanghai Key Laboratory of Chemical Biology School of PharmacyEast China University of Science&TechnologyShanghai 200237China Shanghai Key Laboratory of New Drug Design State Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science&TechnologyShanghai 200237China

Human dihydroorotate dehydrogenase(DHODH) is a viable target for the development of therapeutics to treat cancer and immunological diseases, such as rheumatoid arthritis(RA), psoriasis and multiple sclerosis(MS). Herein, a series of acrylamide-based novel DHODH inhibitors as potential RA treatment agents were designed and synthesized. 2-Acrylamidobenzoic acid analog 11 was identified as the lead compound for structureeactivity relationship(SAR) studies. The replacement of the phenyl group with naphthyl moieties improved inhibitory activity significantly to double-digit nanomolar *** structure optimization revealed that an acrylamide with small hydrophobic groups(Me, Cl or Br)at the 2-position was preferred. Moreover, adding a fluoro atom at the 5-position of the benzoic acid enhanced the potency. The optimization efforts led to potent compounds 42 and 53-55 with IC50 values of 41, 44, 32, and 42 nmol/L, respectively. The most potent compound 54 also displayed favorable pharmacokinetic(PK) profiles and encouraging in vivo anti-arthritic effects in a dose-dependent manner.

关键词： DHODH De novo pyrimidine biosynthesis DHODH inhibitors Acrylamide derivatives Rheumatoid arthritis

Fabrication and characterization of DDAB/PLAalginate composite

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Fabrication and characterization of DDAB/PLAalginate composi...

Uniform-sized DDAB-PLA microparticles as vaccine adjuvant

第十三届全国免疫学学术大会

作者： tingyuan yang Meiyang yang Lianyan Wang Institute of Process Engineering Chinese Academy of Science

The most effective method to reduce chronic hepatitis B virus infection is the universal implementation of *** this study, novel antigen-loaded DDAB/PLA(didodecyldimethylammoniumbromide/poly(lactic acid)) nanoparticles(NPs)-alginate composite microcapsules were developed as a single-shot *** hepatitis B surface antigen(HBsAg)-loaded DDAB/PLA NPs were successfully encapsulated into alginate microcapsules by a modified spray-solidification *** antigen-loaded DDAB/PLA NPsalginate composite microcapsules were prepared under these optimal conditions: the size of composite microcapsules was 24.25 mm, the Span value was 1.627, and the encapsulation efficiency of HBsAg was 68.4%.The obtained microcapsules were spherical gel microparticles with excellent dispersity and narrow size *** vitro release profile indicated a slow release rate of encapsulated HBsAg especially in phosphate buffered saline *** microcapsules showed little toxicity in *** vaccine delivery system could induce stronger immune responses by a single shot, which exhibited much higher cytokine secretion levels closely related to cellular immunity and comparable IgG titers to the traditional aluminum-adjuvanted vaccine with three shots.

关键词： microcapsules single-shot vaccine

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Uniform-sized DDAB-PLA microparticles as vaccine adjuvant

基于可生物降解纳微颗粒的单剂免疫疫苗研究进展

第十三届全国免疫学学术大会

作者： Ting Lu Fumin Hu tingyuan yang Lianyan Wang Guanghui Ma State Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences University of Chinese Academy of Sciences

The FDA-approved biodegradable poly(lactic acid)(PLA) as vaccine adjuvant has attracted the researcher’s attention during recent years. Didodecyldimethylammonium bromide(DDAB) is a kind of cationic surfactant which can endow positive charge to the microparticles(MPs). We fabricated DDAB-PLA(DP) MPs and adsorbed hepatitis B surface antigen(HBsAg) as vaccine and evaluated the immune responses both in vitro and in vivo. Herein, 1.0 μm DP MPs with positive surface charge and narrow size distribution were fabricated by the premixed membrane emulsification method. The MPs can adsorb HBsAg through simple electrostatic interaction. The vaccine formulations can cause DCactivation with up-regulated co-stimulatory and MHC molecules(CD86, MHC Ⅰ, and MHC Ⅱ), and enhance antigen cross-presentation. Animal experiments showed that the DP group induced considerable antigen-specific IgG compared to the commercially available aluminum HBV vaccine. Moreover, after boost immunization, the DP group induced a higher level of IgG than the aluminum group. Furthermore, the vaccine formulations exhibited favorable biocompatibility for BMDCs viability. In conclusion, DDAB-PLA microparticles could be a potential adjuvant for new vaccine development.

关键词： microparticles HBsAg vaccine adjuvant immune response

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过程工程学报 2017年第5期17卷 893-902页

作者：杨美洋王连艳杨婷媛阎雪莹黑龙江中医药大学药学院黑龙江哈尔滨150040 中国科学院过程工程研究所生化工程国家重点实验室北京100190

接种疫苗是防控传染病的有效手段之一,多年来,人们一直致力于疫苗的研究与开发.传统疫苗通常需多次免疫才能达到良好的免疫效果,偏远地区漏种情况严重,导致全球每年约有1亿儿童因不能按时接种疫苗而感染发病甚至死亡.近年来,研究者们通... 详细信息

接种疫苗是防控传染病的有效手段之一,多年来,人们一直致力于疫苗的研究与开发.传统疫苗通常需多次免疫才能达到良好的免疫效果,偏远地区漏种情况严重,导致全球每年约有1亿儿童因不能按时接种疫苗而感染发病甚至死亡.近年来,研究者们通过对缓、控释递送系统的研究,开发单剂疫苗,以提高疫苗接种覆盖率、有效防控传染病.本工作主要对单剂疫苗的历史发展过程、基于可生物降解纳微颗粒的单剂疫苗的性质与调控、纳微颗粒单剂疫苗面临的挑战进行概述.

关键词：单剂免疫纳微颗粒免疫效应抗原释放调控

切口设计及修复情况对上前牙美学区显微根尖手术术后牙龈退缩影响的回顾性研究

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南京医科大学学报（自然科学版） 2024年第7期44卷 941-946,984页

作者：王轲卢伟杨菁菁颜廷元李中武南京医科大学附属口腔医院牙体牙髓病科江苏南京210029 南京医科大学附属口腔医院牙周病科江苏南京210029 南京医科大学附属口腔医院黏膜科江苏南京210029 南京医科大学附属口腔医院口腔颌面外科江苏南京210029

目的:研究切口类型及修复体对上前牙美学区显微根管外科手术(endodontic microsurgery,EMS)后牙龈退缩的影响。方法:纳入53例上前牙美学区需行EMS患者,术后随访1年以上,分析性别、切口类型(沟内切口;龈乳头基部切口)、修复体情况(无修复... 详细信息

目的:研究切口类型及修复体对上前牙美学区显微根管外科手术(endodontic microsurgery,EMS)后牙龈退缩的影响。方法:纳入53例上前牙美学区需行EMS患者,术后随访1年以上,分析性别、切口类型(沟内切口;龈乳头基部切口)、修复体情况(无修复体;有修复体)对上前牙美学区根尖手术后牙龈退缩的影响。结果:按纳入标准,共采集53例患牙临床冠及78例龈乳头数据,统计分析表明,术前及术后1年患牙临床冠高度(H1)、龈乳头高度(H2)及切缘龈乳头距离(H3)存在统计学差异(P <0.05)。性别和切口类型对术后牙龈退缩无显著影响。按修复体有无进行分析,临床冠高度变化(ΔH1)及切缘龈乳头距离变化(ΔH3)均有统计学意义(P <0.05)。结论:上前牙美学区患牙显微根尖手术术后存在一定程度牙龈退缩,修复体的存在会使牙龈退缩加重,影响前牙区美学效果。

关键词：上前牙美学区显微根尖手术牙龈退缩沟内切口龈乳头基部切口

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